TABLE 1.
Clinical characteristics of patients at the time of starting immune checkpoint inhibitors
| Baseline clinical characteristics |
All N = 1,480 |
Non‐liver cancers N = 1,236 |
Liver cancer N = 244 |
P value |
|---|---|---|---|---|
| Male gender (n, %) | 970 (65.5) | 767 (62.1) | 203 (83.2) | <.001 |
| Age (years) | 59.9 ± 13.9 | 60.1 ± 14.0 | 58.9 ± 12.9 | .234 |
| Hemoglobin (g/dL) | 11.5 ± 2.1 | 11.3 ± 2.0 | 12.3 ± 2.1 | <.001 |
| White cell count (x109/L) | 7.8 ± 5.4 | 8.1 ± 5.7 | 6.2 ± 2.9 | <.001 |
| Neutrophil (x109/L) | 5.6 ± 4.1 | 5.8 ± 4.3 | 4.5 ± 2.7 | <.001 |
| Lymphocyte (x109/L) | 1.2 ± 1.1 | 1.3 ± 1.2 | 1.1 ± 0.5 | .001 |
| Eosinophil (x109/L) | 0.2 ± 0.3 | 0.2 ± 0.4 | 0.2 ± 0.2 | .028 |
| Monocyte (x109/L) | 0.6 ± 0.4 | 0.6 ± 0.4 | 0.5 ± 0.2 | <.001 |
| Platelet (x109/L) | 254.1 ± 131.9 | 266.0 ± 132.6 | 193.5 ± 110.2 | <.001 |
| International normalized ratio | 1.1 ± 0.2 | 1.1 ± 0.2 | 1.2 ± 0.2 | <.001 |
| Missing (%) | 10.5 | 11.9 | 3.3 | |
| Albumin (g/L) | 36.2 ± 6.7 | 36.1 ± 6.7 | 36.4 ± 6.6 | 0565 |
| Total bilirubin (μmol/L) | 15.1 ± 38.8 | 11.3 ± 28.3 | 34.3 ± 68.4 | <.001 |
| Alanine aminotransferase (U/L) | 23.0 (14.0 ‐ 38.0) | 21.0 (13.0 ‐ 33.0) | 44.0 (29.0 ‐ 76.0) | <.001 |
| Aspartate aminotransferase (U/L) | 30.0 (21.0 ‐ 53.0) | 27.0 (20.0 ‐ 38.0) | 66.5 (38.0 ‐ 160.8) | <.001 |
| Missing (%) | 33.6 | 38.1 | 10.7 | |
| Creatinine (μmol/L) | 78.7 ± 42.6 | 77.9 ± 44.6 | 82.5 ± 30.5 | .124 |
| Alpha‐fetoprotein (μg/L) | 3.9 (2.4 ‐ 78.8) | 2.7 (1.9 ‐ 4.1) | 387.1 (13.4 ‐ 6762.5) | <.001 |
| Missing (%) | 57.4 | 68.6 | 0.4 | |
| Positive HBsAg (n, %) a | 240 (18.1) | 86 (7.6) | 154 (77.8) | <.001 |
| Missing (%) | 10.3 | 8.6 | 18.9 | |
| Positive anti‐HCV (n, %) a | 13 (2.1) | 3 (0.7) | 10 (6.2) | <.001 |
| Missing (%) | 59.0 | 64.0 | 33.6 | |
| Use of ICIs b | ||||
| PD‐1 Antibody | ||||
| Pembrolizumab | 838 (56.6) | 730 (59.1) | 108 (44.3) | <.001 |
| Nivolumab | 620 (41.9) | 457 (37.0) | 163 (66.8) | <.001 |
| Spartalizumab | 2 (0.1) | 2 (0.2) | 0 (0) | 1.000 |
| PD‐L1 Antibody | ||||
| Atezolizumab | 89 (6.0) | 89 (7.2) | 0 (0) | <.001 |
| Avelumab | 3 (0.2) | 3 (0.2) | 0 (0) | 1.000 |
| Durvalumab | 3 (0.2) | 1 (0.1) | 2 (0.8) | .072 |
| CTLA‐4 Antibody | ||||
| Ipilimumab | 138 (9.3) | 70 (5.7) | 68 (27.9) | <.001 |
| Tremelimumab | 3 (0.2) | 0 (0) | 3 (1.2) | .004 |
| Type of ICIs | ||||
| PD‐1 alone | 1,248 (84.3) | 1,075 (87.0) | 173 (70.9) | <.001 |
| PD‐L1 alone | 84 (5.7) | 84 (6.8) | 0 (0) | |
| CTLA‐4 alone | 3 (0.2) | 3 (0.2) | 0 (0) | |
| CTLA‐4 ± PD‐1/PD‐L1 | 145 (9.8) | 74 (6.0) | 71 (29.1) | |
Alanine aminotransferase, aspartate aminotransferase, alpha‐fetoprotein, and carcinoembryonic antigen were expressed in median (interquartile range), whereas other continuous variables were expressed in mean ± standard deviation. Hypothesis tests compared patients who developed and did not develop liver cancer. Qualitative and quantitative differences between subgroups were analyzed by chi‐squared or Fisher's exact tests for categorical parameters and Student's t test or Mann‐Whitney test for continuous parameters, as appropriate.
Abbreviations: anti‐HCV, antibody to hepatitis C virus; HBsAg, hepatitis B surface antigen; ICIs, immune checkpoint inhibitors.
Percentages were based on non‐missing data.
One patient may use more than one type of ICIs during follow‐up.